Compositions and methods for the treatment of graft versus host disease

Abstract

This application is directed to methods of treating Graft versus Host Disease (GvHD), specifically acute GvHD and acute gastrointestinal GvHD, using apraglutide.

1 . (canceled) 
     
     
         2 . A method of treating or preventing Graft versus Host Disease GvHD) in a subject, the method comprising administering to the subject apraglutide, or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 2 , wherein the GvHD is acute GvHD or chronic GvHD. 
     
     
         4 . The method of  claim 2 , wherein the GvHD is acute gastrointestinal GvHD. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 2 , wherein the GvHD is steroid-refractory or steroid-naïve. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 2 , wherein the GvHD is grade II-IV GvHD according to the MAGIC scale. 
     
     
         9 . The method of  claim 2 , wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered to the subject:
 (a) prior to the subject being administered a transplant; or   (b) prior the subject being administered radiation therapy, chemotherapy, or radiomimetic therapy in connection with a transplant.   
     
     
         10 . The method of  claim 2 , wherein the subject has been previously administered a transplant, wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered to the subject after the subject has been administered a transplant. 
     
     
         11 . The method of  claim 2 , wherein the subject has been previously administered radiation therapy, chemotherapy, radiomimetic therapy or any combination thereof in connection with a transplant, preferably wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered to the subject after the subject has been administered radiation therapy, chemotherapy radiomimetic therapy or any combination thereof. 
     
     
         12 . The method of  claim 2 , wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered to the subject after the subject has been administered radiation therapy, chemotherapy radiomimetic therapy or any combination thereof and prior to the subject being administered a transplant. 
     
     
         13 . The method of  claim 2 , wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered to the subject:
 (a) concurrently with a transplant; or   (b) concurrently with a radiation therapy, a chemotherapy, a radiomimetic therapy, or any combination thereof in connection with a transplant.   
     
     
         14 . The method of  claim 2 , wherein the administration of apraglutide, or pharmaceutically acceptable salt thereof, prevents and/or attenuates a reduction in colon length in a subject following:
 (a) a transplant;   (b) a conditioning therapy and a transplant.   
     
     
         15 . The method of  claim 2 , wherein:
 a) the subject is being or has been administered a transplant, and the transplant comprises hematopoietic stem cells derived from bone marrow, peripheral blood, umbilical cord blood or any combination thereof, wherein the transplant comprises T-cells, wherein the T-cells are chimeric antigen receptor (CAR) T-cells; or   b) the subject is being or has been administered a radiation therapy, and the radiation therapy comprises total body irradiation.   
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 2 , wherein the pharmaceutically acceptable salt of apraglutide is the sodium salt of apraglutide. 
     
     
         18 . The method of  claim 2 , wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered by subcutaneous injection. 
     
     
         19 . The method of  claim 2 , wherein the apraglutide, or pharmaceutically acceptable salt thereof, is administered in an amount of:
 a) between about 1 mg to about 10 mg; or   b) about 2.5 mg, about 5 mg, or about 10 mg.   
     
     
         20 .- 22 . (canceled) 
     
     
         23 . The method of  claim 2 , wherein:
 (a) the subject has a body weight of less than about 50 kg and the apraglutide, or pharmaceutically acceptable salt thereof, is administered in an amount of about 2.5 mg;   (b) the subject has a body weight of about 50 kg to about 60 kg and the apraglutide, or pharmaceutically acceptable salt thereof, is administered in an amount of about 2.5 mg or about 5 mg;   (c) the subject has a body weight of about 60 kg to about 80 kg and the apraglutide, or pharmaceutically acceptable salt thereof, is administered in an amount of about 4 mg or about 7.5 mg; or   (d) the subject has a body weight of greater than about 80 kg and the apraglutide, or pharmaceutically acceptable salt thereof, is administered in an amount of about 5 mg or about 10 mg.   
     
     
         24 . The method of  claim 2 , wherein the subject is being or has been administered a transplant, and the transplant is:
 (a) an allogeneic transplant; or   (b) autologous transplant.   
     
     
         25 . The method of  claim 2 , wherein the subject has been previously administered at least one anti-GvHD therapy, wherein the at least one anti-GvHD therapy comprises steroid therapy. 
     
     
         26 . A method of treating or preventing:
 a) acute Graft versus Host Disease (GvHD);   b) late acute GvHD;   c) acute gastrointestinal GvHD;   d) steroid-refractory GvHD;   e) steroid-naïve GvHD;   f) steroid-refractory acute GvHD;   g) steroid-naïve acute GvHD;   h) steroid-refractory acute gastrointestinal GvHD;   i) steroid-naïve acute gastrointestinal GvHD;   j) chronic GvHD;   k) chronic gastrointestinal GvHD;   l) steroid-refractory chronic gastrointestinal GvHD;   m) steroid-naïve chronic gastrointestinal GvHD;   n) late chronic GvHD;   o) steroid-naïve chronic GvHD;   p) steroid-refractory chronic GvHD;   q) steroid-refractory chronic gastrointestinal GvHD; or   r) Overlap Syndrome   in a subject in need thereof,   the method comprising administering to the subject apraglutide or a pharmaceutically acceptable salt thereof.   
     
     
         27 . A method of treating or preventing Graft versus Host Disease (GvHD) in a subject, the method comprising administering to the subject a combination therapy comprising:
 a) apraglutide, or a pharmaceutically acceptable salt thereof, concurrently with a transplant procedure; or   b) apraglutide, or a pharmaceutically acceptable salt thereof, concurrently with a radiation therapy, a chemotherapy, a radiomimetic therapy, or any combination thereof, in connection with a transplant procedure.